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Author Reply to “Regarding ‘Repair Augmentation of Unstable, Complete Vertical Meniscal Tears With Bone Marrow Venting Procedure: A Prospective, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study’”

      We gratefully thank the Editor for providing us the opportunity to respond to the letter by Wei et al. entitled “Regarding ‘Repair Augmentation of Unstable, Complete Vertical Meniscal Tears With Bone Marrow Venting Procedure: A Prospective, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study’”.
      The authors have explained their concerns about the bone marrow venting procedure in the state of meniscus healing. We appreciated their feedback on our study and the opportunity to discuss meniscus healing in reference to anterior cruciate ligament reconstruction and bone marrow element stimulation. Similar observations to ours were made in an independent study by Dean et al.
      • Dean C.S.
      • Chahla J.
      • Matheny L.M.
      • Mitchell J.J.
      • LaPrade R.F.
      Outcomes after biologically augmented isolated meniscal repair with marrow venting are comparable with those after meniscal repair with concomitant anterior cruciate ligament reconstruction.
      Additionally, at least two randomized clinical trials investigating the influence on meniscal healing of bone marrow venting procedures are ongoing (NCT05053646,NCT04775004).
      As the authors said, studies have demonstrated correlation with better meniscus healing after ACL reconstruction compared with ACL-deficient knee.
      • Korpershoek J.V.
      • de Windt T.S.
      • Vonk L.A.
      • Krych A.J.
      • Saris D.B.F.
      Does anterior cruciate ligament reconstruction protect the meniscus and its repair? A systematic review.
      ,
      • Carlson Strother C.R.
      • Saris D.B.F.
      • Verdonk P.
      • Nakamura N.
      • Krych A.J.
      Biological augmentation to promote meniscus repair: from basic science to clinic application—State of the art.
      We agree with the authors that reestablishment of proper knee kinematics after ACL reconstruction is correlated with better meniscus healing and lower retear rate. Some studies showed significant differences in anterior shift and external rotation during anterior tibial translation in ACL-deficient knee.
      • Klon W.
      • Domżalski M.
      • Malinowski K.
      • Sadlik B.
      Translation and rotation analysis based on stress MRI for the diagnosis of anterior cruciate ligament tears.
      ,
      • Ma C.B.
      • Haughom B.
      • Souza R.
      • Schairer W.
      • Li X.
      • Horvis K.
      Paper # 184: Evaluating rotational kinematics of the knee in ACL ruptured and healthy patients using 3.0 Tesla magnetic resonance imaging.
      We are confident that changes of knee kinematics cause secondary microinjuries to knee structures (i.e., meniscus)
      • von Eisenhart-Rothe R.
      • Bringmann C.
      • Siebert M.
      • et al.
      Femoro-tibial and menisco-tibial translation patterns in patients with unilateral anterior cruciate ligament deficiency—A potential cause of secondary meniscal tears.
      ,
      • Arner J.W.
      • Irvine J.N.
      • Zheng L.
      • et al.
      The effects of anterior cruciate ligament deficiency on the meniscus and articular cartilage: A novel dynamic in vitro pilot study.
      and thus, in our opinion, interrupt healing of the repaired meniscus.
      We also agree with the authors that postoperative rehabilitation is an important factor influencing meniscal and cartilage healing. Many experimental studies provided evidence that changes in hydrostatic pressure load increases the production of proteoglycans and glycosaminoglycan
      • Hodder E.
      • Guppy F.
      • Covill D.
      • Bush P.
      The effect of hydrostatic pressure on proteoglycan production in articular cartilage in vitro: A meta-analysis.
      (in articular cartilage), as well as boosts the replication rate in chondrocytes.
      • Correia C.
      • Pereira A.L.
      • Duarte A.R.C.
      • et al.
      Dynamic culturing of cartilage tissue: The significance of hydrostatic pressure.
      On the contrary, variable rehabilitation protocols were studied (no weight bearing and restricted motion vs. full weight bearing and full range of motion), and no significant difference on the rate of successful meniscal healing was noted.
      • O’Donnell K.
      • Freedman K.B.
      • Tjoumakaris F.P.
      Rehabilitation Protocols After Isolated Meniscal Repair: A Systematic Review.
      ,
      • Fried J.W.
      • Manjunath A.K.
      • Hurley E.T.
      • Jazrawi L.M.
      • Strauss E.J.
      • Campbell K.A.
      Return-to-play and rehabilitation protocols following isolated meniscal repair—A systematic review.
      Indeed, rehabilitation principles have taken steps forward, but the ideal conditions allowing for the successful healing of a repaired meniscus remains to be fully elucidated.
      We suggest that even a short release of growth factors (bone tunnel drilling, bone marrow venting procedures, or a growth factor injections) could provide increased healing potential. In animal models, Koch et al. showed macroscopical and histological enhanced regeneration of teared meniscus by single bone marrow aspirate concentrate injection.
      • Koch M.
      • Hammer S.
      • Fuellerer J.
      • et al.
      Bone marrow aspirate concentrate for the treatment of avascular meniscus tears in a one-step procedure—Evaluation of an in vivo model.
      Also, Abdel-Hamid et al. made a similar observation.
      • Abdel-Hamid M.
      • Hussein M.R.
      • F. Ahmad A
      • Elgezawi E.M.
      Enhancement of the repair of meniscal wounds in the red-white zone (middle third) by the injection of bone marrow cells in canine animal model: Improved healing of meniscal tears after BM injection.
      If a single injection of bone marrow aspirate significantly increases the potential of meniscal healing in animal models, the same mechanism could play a role in human meniscus healing. Girolamo et al. presented increased PDGF concentration after ACL reconstruction in joint fluid 30 min after the end of the surgical procedure.
      • de Girolamo L.
      • Galliera E.
      • Volpi P.
      • et al.
      Why menisci show higher healing rate when repaired during ACL reconstruction? Growth factors release can be the explanation.
      Galliera et al. measured VEGF and VEGFR2 levels after 30 min of arthroscopy in knee joint fluid. They showed significantly higher levels of those factors in the ACL reconstruction group compared to the control group.
      • Galliera E.
      • De Girolamo L.
      • Randelli P.
      • et al.
      High articular levels of the angiogenetic factors VEGF and VEGF-receptor 2 as tissue healing biomarkers after single bundle anterior cruciate ligament reconstruction.
      However, both studies quoted by the authors, have some weak points. The first is joint drainage—allowing for “cytokine mixture” escape form the joint. The second is the collection of joint fluid sample at a single time point (30 minutes after the end of surgical procedure). Such results do not allow us to draw any conclusion on the process of growth factor concentration kinetics. On the contrary, the study by Beckmann et al., which evaluated abrasion arthroplasty provide additional data.
      • Beckmann R.
      • Lippross S.
      • Hartz C.
      • et al.
      Abrasion arthroplasty increases mesenchymal stem cell content of postoperative joint effusions.
      They studied mesenchymal stem cell content and growth factor concentration in postoperative joint effusions (samples were collected after 21 h ± 2.5 h postoperation). They noticed a significantly increased concentration of TGF-β, IGF-1, mononuclear cells, and abrasion arthroplasty released cells with phenotypes typical to mesenchymal stem cells. Interestingly, those cells, expanded in high-density cultures, showed positive staining for markers indicating the chondrogenic differentiation. Similarly, techniques allowing for recruitment of synovial mesenchymal cells is a synovial abrasion. One cannot expect that this technique will recruit a massive number of mesenchymal stem cells or cause a massive release of growth factors into the joint. Despite this, it is successfully applied into the clinical setting, allowing for meniscal healing even with no suture repair in selected patients.
      • Shelbourne K.D.
      • Gray T.
      Meniscus tears that can be left in situ, with or without trephination or synovial abrasion to stimulate healing.
      ,
      • Uchio Y.
      • Ochi M.
      • Adachi N.
      • Kawasaki K.
      • Iwasa J.
      Results of rasping of meniscal tears with and without anterior cruciate ligament injury as evaluated by second-look arthroscopy.
      In our procedure described in the article,
      • Kaminski R.
      • Kulinski K.
      • Kozar-Kaminska K.
      • Wasko M.K.
      • Langner M.
      • Pomianowski S.
      Repair augmentation of unstable, complete vertical meniscal tears with bone marrow venting procedure: A prospective, randomized, double-blind, parallel-group, placebo-controlled study.
      we perform bone marrow venting as a last step during arthroscopy, with no drainage to the joint. We believe, this simple measure may prevent rinsing of the growth factors and cells released.
      In conclusion, according to multiple studies, we believe that meniscal healing is a multifactorial process, equally requiring biologic and kinematic factors. Restoring proper knee biomechanics plays a pivotal role. Nowadays, there is contradictory data on the optimal rehabilitation protocol. We are convinced the best possible protocol should be guided by biomechanics, but more studies are necessary to resolve this issue. We also believe that proper surgical technique and appliance of additional techniques that may lead to significantly higher meniscus healing rate (such as bone marrow venting, recruitment of mesenchymal stem cells) is beneficial to the patient. Despite the progress in orthopedics and basic sciences, a lot of questions remain unanswered. Does every patient with a meniscal tear have disturbed knee kinematics? Do we require more sensitive diagnostic tools? What is the optimal timeframe for growth factors and mesenchymal stem cell release? Is a high concentration of these factors in joint fluid necessary? Or perhaps, the process of meniscal healing is more similar to wound healing or morphogenesis, with local gradient of growth factors that is interpreted by target cells, according to preset concentration thresholds? Further studies are required to enable us to understand the process of meniscal healing. Hopefully, new answers will benefit our patients achieving 100% meniscal healing rate with 0% of retears in the future.

      Supplementary Data

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